A gut-derived <i>Streptococcus salivarius</i> produces the novel nisin variant designated nisin G and inhibits <i>Fusobacterium nucleatum</i> in a model of the human distal colon microbiome

<i>Fusobacterium nucleatum</i> is a human pathogen associated with intestinal conditions including colorectal cancer. Screening for gut-derived strains that exhibit anti-<i>F</i>. <i>nucleatum</i> activity <i>in vitro</i> revealed <i>Streptococcus salivarius</i> DPC6487 as a strain of interest. Whole-genome sequencing of <i>S. salivarius</i> DPC6487 identified a nisin operon with a novel structural variant designated nisin G. The structural nisin G peptide differs from the prototypical nisin A with respect to seven amino acids (Ile4Tyr, Ala15Val, Gly18Ala, Asn20His, Met21Leu, His27Asn, and His31Ile), including differences that have not previously been associated with a natural nisin variant. The nisin G gene cluster consists of <i>nsgGEFABTCPRK</i> with transposases encoded between the nisin G structural gene (<i>nsgA</i>) and <i>nsgF</i>, notably lacking an equivalent to the <i>nisI</i> immunity determinant. <i>S. salivarius</i> DPC6487 exhibited a narrower spectrum of activity <i>in vitro</i> compared to the nisin A-producing <i>Lactococcus lactis</i> NZ9700. Nisin G-producing <i>S. salivarius</i> DPC6487 demonstrated the ability to control <i>F. nucleatum</i> DSM15643 in an <i>ex vivo</i> model colonic environment while exerting minimal impact on the surrounding microbiota. The production of this bacteriocin by a gut-derived <i>S. salivarius</i>, its narrow-spectrum activity, and its anti-<i>F. nucleatum</i> activity in a model colonic environment indicates that this strain merits further attention with a view to harnessing its probiotic potential.IMPORTANCE<i>Fusobacterium nucleatum</i> is a human pathogen associated with intestinal conditions, including colorectal cancer, making it a potentially important therapeutic target. Bacteriocin-producing probiotic bacteria demonstrate the potential to target disease-associated taxa <i>in situ</i> in the gut. A gut-derived strain <i>Streptococcus salivarius</i> DPC6487 was found to demonstrate anti-<i>F</i>. <i>nucleatum</i> activity, which was attributable to a gene encoding a novel nisin variant designated nisin G. Nisin G-producing <i>S. salivarius</i> DPC6487 demonstrated the ability to control an infection of <i>F. nucleatum</i> in a simulated model of the human distal colon while exerting minimal impact on the surrounding microbiota. Here, we describe this nisin variant produced by <i>S. salivarius</i>, a species that is frequently a focus for probiotic development. The production of nisin G by a gut-derived <i>S. salivarius</i>, its narrow-spectrum activity against <i>F. nucleatum</i>, and its anti-<i>F</i>. <i>nucleatum</i> activity in a model colonic environment warrants further research to determine its probiotic-related applications.